By
Mark Wanner

In addition to sequence, three-dimensional (3D) genome structure contributes to vital functions, including transcriptional regulation, DNA replication and DNA methylation. To study genome structure and function, several research methods have been developed based on chromosome conformation capture (3C) techniques, including Hi-C, which allows analysis on a genomic scale. The technology is currently generating massive amounts of data on 3D chromatin structure and interactions in living cells. Analysis is made challenging by the amount and diversity of the data being produced.

In “HSA: integrating multi-track Hi-C data for genome-scale reconstruction of 3D chromatin structure,” published March 2 in Genome Biology, JAX Assistant Professor Zhengqing Ouyang, Ph.D., members of his lab and collaborators present HSA, a computational tool that analyzes diverse Hi-C data sets—such as those using different restriction enzymes—to reconstruct 3D chromatin structure robustly and accurately, with significant improvements, including higher resolutions.

In testing and validating HSA, Ouyang et al found striking structural consistencies across different human cell types, suggesting that some 3D conformations remain constant despite the overall dynamic nature of the genome. The finding provides additional areas to explore, including studying how and why chromatin generates different 3D conformations across cell types while maintaining areas of topology that don’t change, and extending their analysis to more cell types to derive the principal rules underlying 3D genome folding.